Background: The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery. Methods: This is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated. Results: The total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks [range, 22.6–40.0] and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir. Conclusion Our data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.

Background: Though antenatal magnesium sulfate (MgSO4 ) is widely used for fetal neuroprotection, suspicions about the long-term neuroprotection of antenatal MgSO4 have been raised. Methods: We investigated short- and long-term outcomes of antenatal MgSO4 use for 468 infants weighing < 1,500 g with a gestational age of 24–31 weeks. Results: Short-term morbidities and the risk of developmental delay, hearing loss, and cerebral palsy at a corrected age of 18–24 months and 3 years of age did not decrease in the MgSO4 group (infants who were exposed to MgSO4 for any purpose) or neuroprotection group (infants who were exposed to MgSO4 for fetal neuroprotection) compared with the control group (infants who were not exposed to MgSO4 ). The z-scores of weight, height, and head circumference did not increase in the MgSO4 group or neuroprotection group compared with the control group. Conclusion Antenatal MgSO4 including MgSO4 for neuroprotection did not have beneficial effects on long-term neurodevelopmental and growth outcomes.

Objective: We aimed to present the study design and baseline cross-sectional participant characteristics of biobank innovations for chronic cerebrovascular disease with Alzheimer’s disease study (BICWALZS) participants. Methods: A total of 1,013 participants were enrolled in BICWALZS from October 2016 to December 2020. All participants underwent clinical assessments, basic blood tests, and standardized neuropsychological tests (n=1,013). We performed brain magnetic resonance imaging (MRI, n=817), brain amyloid positron emission tomography (PET, n=713), single nucleotide polymorphism microarray chip (K-Chip, n=949), locomotor activity assessment (actigraphy, n=200), and patient-derived dermal fibroblast sampling (n=175) on a subset of participants. Results: The mean age was 72.8 years, and 658 (65.0%) were females. Based on clinical assessments, total of 168, 534, 211, 80, and 20 had subjective cognitive decline, mild cognitive impairment (MCI), Alzheimer’s dementia, vascular dementia, and other types of dementia or not otherwise specified, respectively. Based on neuroimaging biomarkers and cognition, 199, 159, 78, and 204 were cognitively normal (CN), Alzheimer’s disease (AD)-related cognitive impairment, vascular cognitive impairment, and not otherwise specified due to mixed pathology (NOS). Each group exhibited many differences in various clinical, neuropsychological, and neuroimaging results at baseline. Baseline characteristics of BICWALZS participants in the MCI, AD, and vascular dementia groups were generally acceptable and consistent with 26 worldwide dementia cohorts and another independent AD cohort in Korea. Conclusion The BICWALZS is a prospective and longitudinal study assessing various clinical and biomarker characteristics in older adults with cognitive complaints. Details of the recruitment process, methodology, and baseline assessment results are described in this paper.

Objective: We investigated prenatal sonographic characteristics of esophageal atresia (EA) with advancing gestation. We focused on the degree of polyhydramnios and the stomach shape. Methods: This study included 27 EA cases (EA group) and 81 idiopathic polyhydramnios cases (non-EA group). The non-EA group consisted of cases without any fetal structural anomaly, musculoskeletal disorder, chromosomal abnormality, or maternal diabetes. Both groups included only singleton pregnancies. Amniotic fluid index (AFI) and width/length (W/L) ratio as well as the product of width and length (W×L) of stomach were serially assessed during gestation and compared between the 2 groups. To predict EA using W/L ratio and W×L, receiver operating characteristic curve analysis was performed. Results: Polyhydramnios was evident in 77.8% of EA cases. We observed 25.9% and 22.2% EA cases with an absent stomach and a small visible stomach, respectively. After 28 weeks, the EA group manifested significantly higher AFI than the non-EA group. After 32 weeks, W/L ratio in the EA group tended to be lower than that in the non-EA group (32–36 weeks: 1.36 vs. 1.72, P=0.092; >36 weeks: 1.43 vs. 1.63, P=0.024). To predict EA, the calculated area under the curve for W/L ratio was 0.651 after 32 weeks. The diagnosis of EA using a cut-off value of W/L ratio <1.376 showed sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio to be 84.6%, 52.9%, 1.796, and 0.081, respectively. Conclusion A low W/L ratio of stomach after 32 weeks with progressive idiopathic polyhydramnios may be used to predict EA.

Objective: To evaluate the effects of maternal body mass index (BMI) and plurality on maternal and umbilical cord serum magnesium levels after antenatal magnesium sulfate treatment. Methods: This was a retrospective cohort analysis of 135 women treated with antenatal magnesium sulfate at less than 32 weeks of gestation between January 2012 and June 2018. Subjects were stratified into groups according to maternal BMI (group I [18.5–22.9 kg/m²], group II [23.0–24.9 kg/m²], and group III [≥25.0 kg/m²]) and plurality (singleton and twin). Univariable and multivariable analyses were performed to compare the umbilical cord serum magnesium levels between the groups. Results: Maternal serum magnesium levels were not significantly different between the maternal BMI groups and singleton and twin pregnancies. Umbilical cord serum magnesium levels were significantly different among the maternal BMI groups (3.3±1.2 mg/dL in group I, 3.3±1.2 mg/dL in group II, and 4.0±1.4 mg/dL in group III, P=0.003). The trend of increase in magnesium levels was statistically significant (P=0.001, Jonckheere-Terpstra test). Umbilical cord serum magnesium levels were not significantly different according to plurality. However, in the multivariable analysis, maternal BMI and plurality were not significantly associated with umbilical cord serum magnesium levels after adjusting for indication and total dose of magnesium sulfate treatment, gestational age at delivery, mode of delivery, neonatal sex, and birth weight. Conclusion Maternal BMI and plurality were not significantly associated with maternal or umbilical cord serum magnesium levels after exposure to antenatal magnesium sulfate treatment.

Objectives: This study determines the effects of comorbidity of mood disorder and alcohol use disorder on suicide behavior. Methods: We converted data from the electronic medical records of one university hospital into a common data model and utilized it in our analysis. We selected 9551 patients with diagnosis codes of mood disorders or alcohol use disorders and divided them into three groups: mood disorder (MD) only, alcohol use disorder (AUD) only, and comorbidity of mood disorder and alcohol use disorder (MD+AUD). The mood disorder group was also subgrouped with depressive (DD) or bipolar affective disorder (BD) groups, and the comorbidity group was classified in the same way. Then, we applied logistic regression analysis to assess the risk of suicide attempts between the diagnostic groups. Subgroup analysis according to age also was conducted. Results: The MD+AUD group had 2.7 (odd ratio [OR]=2.70, 95% confidence intervals [CI]=1.91– 3.81, p<0.0001) and the DD+AUD group had 2.78 (OR=2.78, 95% CI=1.95–3.98, p<0.0001) times higher risk of suicide attempts than the MD only and DD only group, respectively. Furthermore, according to the age subgroup, the risk of suicide attempts was the highest (OR=5.17, 95% CI=2.35–11.40, p<0.0001) in the DD+AUD group for those aged 40–59. There were no significant results in BD. Conclusion The results showed that the comorbidity of mood disorder and alcohol use disorder could increase suicide risk. This study suggested that alcohol use behavior needs to be assessed as well as mood symptoms for suicide prevention.

Objectives: This study determines the effects of comorbidity of mood disorder and alcohol use disorder on suicide behavior. Methods: We converted data from the electronic medical records of one university hospital into a common data model and utilized it in our analysis. We selected 9551 patients with diagnosis codes of mood disorders or alcohol use disorders and divided them into three groups: mood disorder (MD) only, alcohol use disorder (AUD) only, and comorbidity of mood disorder and alcohol use disorder (MD+AUD). The mood disorder group was also subgrouped with depressive (DD) or bipolar affective disorder (BD) groups, and the comorbidity group was classified in the same way. Then, we applied logistic regression analysis to assess the risk of suicide attempts between the diagnostic groups. Subgroup analysis according to age also was conducted. Results: The MD+AUD group had 2.7 (odd ratio [OR]=2.70, 95% confidence intervals [CI]=1.91– 3.81, p<0.0001) and the DD+AUD group had 2.78 (OR=2.78, 95% CI=1.95–3.98, p<0.0001) times higher risk of suicide attempts than the MD only and DD only group, respectively. Furthermore, according to the age subgroup, the risk of suicide attempts was the highest (OR=5.17, 95% CI=2.35–11.40, p<0.0001) in the DD+AUD group for those aged 40–59. There were no significant results in BD. Conclusion The results showed that the comorbidity of mood disorder and alcohol use disorder could increase suicide risk. This study suggested that alcohol use behavior needs to be assessed as well as mood symptoms for suicide prevention.

Rhabdomyoma is the most common fetal cardiac tumor, and its development is related to tuberous sclerosis. Fetal cardiac rhabdomyomas often spontaneously regress in utero or after birth, but large tumors can cause hemodynamic obstruction. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used as an immunosuppressant after organ transplantation. The mTOR inhibitors are well-known to have anti-tumor activity, and they have been used for the treatment of patients with tuberous sclerosis. In the current case, fetal cardiac rhabdomyoma was completely resolved in utero during oral sirolimus treatment in the mother with tuberous sclerosis. This case shows that oral sirolimus therapy in pregnancy may be a treatment for multiple or large fetal cardiac rhabdomyomas.
Female ; Fetal Therapies ; Heart Neoplasms ; Hemodynamics ; Humans ; Mothers ; Organ Transplantation ; Parturition ; Pregnancy ; Pregnant Women ; Rhabdomyoma ; Sirolimus ; Transplants ; Tuberous Sclerosis

OBJECTIVE: Although the conventional prevalence of myotonic dystrophy is 1:8,000, the prevalence in Korean population was recently reported as 1:1,245. With higher domestic result than expected, we aimed to investigate the clinical characteristics of pregnancies complicated by congenital myotonic dystrophy in our institution. METHODS: We have reviewed 11 paired cases of neonates diagnosed with congenital myotonic dystrophy and their mothers between July 2004 and May 2014, with clinical features including maternal history of infertility, prenatal ultrasonographic findings, and neonatal outcomes. Cytosine-thymine-guanine (CTG) repeat expansion in the myotonic dystrophy protein kinase gene of both neonates and their mothers was also examined. RESULTS: None of mother was aware of their myotonic dystrophy traits before pregnancy. History of infertility followed by assisted reproductive technology accounted for 57.1% (4/7). Distinctive prenatal ultrasonographic finding was severe idiopathic polyhydramnios (66.7%, 4/6) with median amniotic fluid index of 43 (range, 37 to 66). In 37.5% (3/8) cases, decreased fetal movement was evident during prenatal ultrasound examination. For neonatal outcomes, more than half (6/11) were complicated with preterm birth and the proportion of 1-minute Apgar score <4 and 5-minute Apgar score <7 was 44.4% (4/9) and 66.7% (6/9), respectively. Most of neonates were admitted to the neonatal intensive care unit (9/10) because of hypotonia with respiratory problems and there was one infant death. Median number of cytosine-thymine-guanine repeats in mothers and neonates was 400 (range, 166 to 1,000) and 1,300 (range, 700 to 2,000), respectively. CONCLUSION: Our data suggest that severe idiopathic polyhydramnios with decreased fetal movement in pregnant women, especially with a history of infertility, requires differential diagnosis of congenital myotonic dystrophy.
Amniotic Fluid ; Apgar Score ; Diagnosis, Differential ; Female ; Fetal Movement ; Humans ; Infant Death ; Infant, Newborn ; Infertility ; Intensive Care, Neonatal ; Mothers ; Muscle Hypotonia ; Myotonic Dystrophy* ; Myotonin-Protein Kinase ; Polyhydramnios ; Pregnancy* ; Pregnant Women ; Premature Birth ; Prenatal Diagnosis ; Prevalence ; Reproductive Techniques, Assisted ; Ultrasonography

OBJECTIVE: With recent advances and frequent use of prenatal ultrasound, the antenatal diagnosis of agenesis of the corpus callosum (ACC) is not rare in obstetrics practices. However, information regarding the long-term neurological outcome remains uncertain. The aim of this study was to investigate clinical outcomes of prenatally diagnosed ACC and to analyze postnatal neurodevelopmental outcomes of ACC neonates born in our single center. METHODS: We retrospectively reviewed 56 cases of prenatally suspected ACC referred to our center. RESULTS: Fifty-six fetuses were diagnosed with ACC, and 12 of those were followed-up in our center until delivery. Of the remaining 44, 7 were delivered after being referred back to the original hospital, 23 were lost to follow-up, and 14 had unknown outcomes. Among all 56, 29 were considered to have isolated ACC and 27 were considered to have non-isolated ACC. Of the 10 live fetuses delivered in our center, four had isolated ACC, three had non-isolated ACC, and the rest had outcomes unrelated to ACC. Neurodevelopmental outcome was followed-up until approximately age 3 years. Of the four with isolated ACC, three (75%) had normal neurodevelopmental outcomes. CONCLUSION: Similar to other studies, the results of our single-center study included positive neurodevelopmental outcomes for those with isolated ACC. However, despite our endeavor to counsel patients with prenatally diagnosed ACC, the delivery rate in our center was quite low. Therefore, larger, multicenter, retrospective studies including long-term neurological development outcomes are crucial and urgently needed to provide better counseling.
Agenesis of Corpus Callosum* ; Corpus Callosum ; Counseling ; Fetus ; Humans ; Infant, Newborn ; Korea* ; Lost to Follow-Up ; Obstetrics ; Prenatal Diagnosis ; Retrospective Studies ; Ultrasonography